丹酚酸A改善ZDF大鼠视网膜病变及其作用机制
作者:
基金项目:

浙江省中医药管理局重点项目(2015ZZ009);浙江中医药大学比较医学创新团队(XTD201301)。


Effect of salvianolic acid A on retinopathy and its mechanism in ZDF rats
Author:
  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献 [19]
  • | | | |
  • 文章评论
    摘要:

    目的 观察丹酚酸A (SAA)对Zucker糖尿病肥胖(ZDF)大鼠视网膜病变的干预作用,探讨SAA可能的作用机制。方法 取7~8周龄雄性ZDF大鼠32只,Purina#5008饲料饲喂4周后,按血糖平均分为模型对照组,SAA高、低剂量组与二甲双胍(Met)组,每组8只。另取同龄雄性ZL大鼠8只作为正常对照。SAA低、高剂量组每日尾静脉注射SAA 0.5 mg/kg、1 mg/kg,Met组每日经口灌胃Met 200 mg/kg,连续给药12周,观察ZDF大鼠白内障发生率和视网膜病理学改变,并检测血糖血脂、糖化血红蛋白(HbA1c)和血清白介素1(IL-1)、IL-6、氧化性低密度脂蛋白(ox-LDL)、丙二醛(MDA)含量和脂蛋白相关磷脂酶A2(Lp-PLA2)的活性,以及尿液中转铁蛋白(TRF)、视黄醇结合蛋白(RBP)的含量。结果 模型对照组大鼠血糖、血脂及HbA1c均上升,糖尿病性白内障发病率68.75%,视网膜基底增厚和微血管病变,血清IL-1、IL-6、ox-LDL和MDA含量和Lp-PLA2活性显著升高,尿液中TRF和RBP含量亦显著升高。给予SAA后,ZDF大鼠白内障发病率降低,视网膜病理学形态有不同程度的改善,血清IL-1、IL-6、ox-LDL、MDA含量和Lp-PLA2活性下降,尿液中TRF、RBP含量亦下降。结论 SAA能改善ZDF大鼠糖尿病视网膜病变,降低白内障发生率,其作用途径可能与抑制慢性炎症、防止脂质过氧化和降低Lp-PLA2活性有关。

    Abstract:

    Objective To observe the intervention effect of salvianolic acid A (SAA) on retinopathy of Zucker diabetic fatty (ZDF) rats and explore the possible action mechanism of SAA to prevent and treat diabetic retinopathy (DR). Methods Thirty-two 7-8-week old ZDF rats were taken and fed with Purina rat chow for 4 weeks. The ZDF rats were equally divided by the blood glucose into model group, 0.5 mg/kg SAA group, 1.0 mg/kg SAA group and metformin (Met) group. 8 Zucker lean (ZL) rats were taken as control group. After 12-week administration, incidence of cataracts and retinal pathology was observed, and levels of GLU, TC and HbA1c in blood, transferrin (TRF) and retinol binding protein (RBP) in urine and levels of interleukin-1 (IL-1), interleukin-6 (IL-6), oxidized low density lipoprotein (ox-LDL), malondialdehyde (MDA) and lipoprotein related phospholipase A2 (Lp-PLA2) activity in serum were measured. Results In the model group, GLU, TC, HbA1c, diabetic cataract incidence rate, retinal basement thickening and microangiopathy appeared in most of the rats. The levels of TRF and RBP in urine and levels of IL-1, IL-6, ox-LDL, MDA in serum were significantly increased, and Lp-PLA2 activity was also significantly increased. After SAA administration, the morbidity rate of cataract was reduced, and retinal pathological changes were improved in different degrees. The levels of TRF, RBP, IL-1, IL-6, ox-LDL, MDA and Lp-PLA2 activity was decreased. Conclusions SAA can slow down the process of diabetic retinopathy in ZDF rats and reduce the incidence of cataract. The mechanisms of action may be related to inhibition of chronic inflammation, prevention of lipid peroxidation and reduction of Lp-PLA2 activity.

    参考文献
    [1] Forouhi NG, Wareham NJ.Epidemiology of diabetes[J]. Medicine (Abingdon), 2014, 42(12):698-702.
    [2] Hammes HP, Feng Y, Pfister F, et al. Diabetic retinopathy:targeting vasoregression[J]. Diabetes, 2011, 60(1):9-16.
    [3] Ferris FL, Nathan DM. Preventing diabetic retinopathy progression[J]. Ophthalmology, 2016, 123(9):1840-1842.
    [4] 张莉, 张维库, 赵莹, 等. 丹酚酸A的研究与进展[J]. 中国中药杂志, 2011, 36(19):2603-2609.
    [5] 鲁珽, 陈方明, 朱科燕, 等. 注射用丹酚酸A防治肝纤维化的实验研究[J]. 中国比较医学杂志, 2014, 24(7):57-62.
    [6] Chien MY, Chuang CH, Chern CM, et al. Salvianolic acid A alleviates ischemic brain injury through the inhibition of inflammation and apoptosis and the promotion of neurogenesis in mice[J].Free Radical Bio Med, 2016, 99:508-519.
    [7] 段惠惠, 黄建梅, 于素云, 等. STZ糖尿病大鼠视网膜病变模型的再评价[J]. 中国比较医学杂志, 2013, 23(5):12-18.
    [8] 陈小真, 戎亦骊, 马全鑫, 等. 糖尿病ZDF大鼠早期微血管并发症的生化指标及病理组织学变化[J]. 中国比较医学杂志, 2016, 26(5):63-70.
    [9] 杨洪亮. 脂蛋白(a), 尿视黄醇结合蛋白与糖尿病视网膜病变的相关性研究[J]. 微量元素与健康研究, 2015, 32(1):13-14.
    [10] 王芳, 徐莉. 内皮细胞损伤及尿微量蛋白与糖尿病视网膜病变的相关性研究[J]. 现代预防医学, 2008, 35(17):3435-3436.
    [11] Chen YH, Chen HS, Tarng DC. More impact of microalbuminuria on retinopathy than moderately reduced GFR among type 2 diabetic patients[J]. Diabetes Care, 2012, 35(4):803-808.
    [12] Van Hecke MV, Dekker JM, Nijpels G, et al. Inflammation and endothelial dysfunction are associated with retinopathy:the Hoorn Study[J]. Diabetologia, 2005, 48(7):1300-1306.
    [13] Spijkerman AMW, Gall MA, Tarnow L, et al. Endothelial dysfunction and low-grade inflammation and the progression of retinopathy in type 2 diabetes[J]. Diabetic Med, 2007, 24(9):969-976.
    [14] Stitt AW, Curtis TM, Chen M, et al. The progress in understanding and treatment of diabetic retinopathy[J]. Prog Retin Eye Res, 2016, 51:156-186.
    [15] Li L, Xu T, Du Y, et al. Salvianolic acid a attenuates cell apoptosis, oxidative stress, Akt and NF-κB activation in angiotensin-Ⅱ induced murine peritoneal macrophages[J]. Curr Pharm Biot Echno, 2016, 17(3):283-290.
    [16] Huang J, Qin Y, Liu B, et al. In silico analysis and experimental validation of molecular mechanisms of salvianolic acid A-inhibited LPS-stimulated inflammation, in RAW264. 7 macrophages[J]. Cell Proliferat, 2013, 46(5):595-605.
    [17] Madsen-Bouterse SA, Kowluru RA. Oxidative stress and diabetic retinopathy:pathophysiological mechanisms and treatment perspectives[J]. Rev Endocr Met Ab Dis, 2008, 9(4):315-327.
    [18] Wilensky RL, Macphee CH. Lipoprotein-associated phospholipase A2 and atherosclerosis[J]. Curr Opin Lipidol, 2009, 20(5):415-420.
    [19] Canning P, Kenny BA, Prise V, et al. Lipoprotein-associated phospholipase A2(Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes[J]. P Natl Acad Sci U S A, 2016, 113(26):7213-7218.
    相似文献
    引证文献
引用本文

马全鑫,陈小真,戎亦骊,黄俊杰,朱科燕,陈诚,施佳君,李园园,陈民利.丹酚酸A改善ZDF大鼠视网膜病变及其作用机制[J].中国比较医学杂志,2017,27(10):40~46.

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2017-04-12
  • 在线发布日期: 2017-10-23